A mutation in the sodium channel is responsible for the association of long QT syndrome and familial atrial fibrillation.
BACKGROUND
Type 3 long-QT syndrome (LQT-3) is caused by gain-of-function mutations in the SCN5A encoding the cardiac sodium channel. Familial atrial fibrillation (AF), previously considered a potassium channelopathy, has recently been related to sodium genetic variants, both in isolated forms and in patients with underlying heart disease.


OBJECTIVE
The purpose of this study was to describe the first family associating LQT-3 and AF due to a gain-of-function mutation in SCN5A and assess the usefulness of the sodium blocker flecainide in individuals with both phenotypes.


METHODS
Complete family screening was performed after identifying a proband showing paroxysmal AF and a long QT interval suggestive of LQT-3. Secondary causes of AF were ruled out in all individuals. Flecainide was used in two patients for LQT-3 diagnosis and therapeutic treatment of AF. Genetic screening was performed by direct sequencing of the exons and exon-intron boundaries of SCN5A.


RESULTS
We identified a three-generation family (eight members), all of them showing long QT intervals. Paroxysmal AF initiated between 20 and 35 years of age in all three adults. The flecainide test led to shortening of the QTc interval. Flecainide was also effective in acutely restoring sinus rhythm. A Y1795C mutation was identified in all members.


CONCLUSIONS
This is the first report showing an association of familial AF and LQT-3 due to a mutation in SCN5A. This finding provides further evidence of the role of SCN5A in AF. We also confirm the usefulness of flecainide in this particular complex phenotype, both as a diagnostic tool for LQT-3 and as an acute treatment for AF.
Benito
Begoña
B
Cardiovascular Genetics Center, Montreal Heart Institute, University of Montreal, Montreal, Canada.
Brugada
Ramon
R
Perich
Rosa Maria
RM
Lizotte
Eric
E
Cinca
Juan
J
Mont
Lluis
L
Berruezo
Antonio
A
Tolosana
José María
JM
Freixa
Xavier
X
Brugada
Pedro
P
Brugada
Josep
J
D000328:Adult; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005424:Flecainide / Q000627:therapeutic use; D020022:Genetic Predisposition to Disease; D006801:Humans; D008133:Long QT Syndrome / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D009154:Mutation; D062554:NAV1.5 Voltage-Gated Sodium Channel; D015222:Sodium Channels / Q000235:genetics*
D000889:Anti-Arrhythmia Agents; D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels; D005424:Flecainide